酸敏感受體TDAG8與ASIC3參與在酸誘發的機械性痛覺過敏感現象;Involvement of proton-sensing receptors TDAG8 and ASIC3 in acid-induced mechanical hyperalgesia

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Title:	酸敏感受體TDAG8與ASIC3參與在酸誘發的機械性痛覺過敏感現象;Involvement of proton-sensing receptors TDAG8 and ASIC3 in acid-induced mechanical hyperalgesia
Authors:	戴士評;Dai,Shih-Ping
Contributors:	生命科學系
Keywords:	酸敏感受體;Proton-sensing receptors
Date:	2015-06-08
Issue Date:	2015-07-30 18:52:13 (UTC+8)
Publisher:	國立中央大學
Abstract:	目前在臨床上認為神經受傷、癌症及關節炎所引發的慢性疼痛是一個很嚴重的問題。而這些發炎的組織所造成的酸化現象被認定為慢性疼痛的重要因子。雖然有肌肉發炎疼痛模式相關研究認為ASIC3及TRPV1參與在hyperalgesic priming上，然而相關機制仍不清楚。在這項研究中，我使用小鼠腳掌皮下注射二次酸模式來探討ASIC3、TRPV1及TDAG8在hyperalgesic priming的功能。實驗結果發現，二次酸注射於野生型小鼠將誘發一個長期 (13天) 的機械性痛覺過敏感現象。而ASIC3-/-及TRPV1-/-小鼠在二次酸注射後縮短痛覺敏感現象的時間。另外，TDAG8則參與在酸所誘發痛覺敏感現象的起始階段中。其中，我們從小分子化合物中發現NSC745885與NSC745887能有效抑制酸、完全弗氏佐劑及神經受損所誘發的痛覺過敏感。更發現NSC745885能有效抑制TDAG8的基因表現及功能。因此，從我實驗結果中可以推論，TDAG8參與在起始痛覺敏感性上，而ASIC3及TRPV1參與在hyperalgesic priming。;Chronic pain induced by nerve injury, cancer and arthritis is a serious clinical problem disturbing many people. Tissue acidosis is a major factor contributing to chronic pain. Although, a previous study in muscle pain model suggested that ASIC3 and TRPV1 are involved in hyperalgesic priming. However, the detailed mechanism for hyperalgesic priming or other factors involved in priming remains unclear. In this study, I used intraplantarly dual acid injection to explore the roles of ASIC3, TRPV1, and TDAG8 in hyperalgesic priming. Dual acid injection in wild-type mice induced a long-term (13 days) mechanical hyperalgesia. Both of ASIC3-/- and TRPV1-/- mice shortened mechanical hyperalgesia after dual acid injection. TDAG8 was involved in the initiation of mechanical hyperalgesia induced by acid. We also found that small molecule compounds, NSC745885 and 887 inhibited mechanical hyperalgesia induced by acid, CFA, or nerve injury. NSC745885 specifically inhibited TDAG8 expression and function. Accordingly, TDAG8 is involved in the initiation of hyperalgesia, whereas ASIC3 and TRPV1 are involved in hyperalgesic priming.
Appears in Collections:	[Graduate Institute of Life Science] Electronic Thesis & Dissertation

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